Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators
A series of 20 histamine Schiff base was synthesised by reaction of histamine, a well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with substituted aldehydes. The obtained histamine Schiff bases were assayed as activators of five selected human (h) CA isozymes, the cytosolic...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2017.1386660 |
| _version_ | 1818314995726811136 |
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| author | Suleyman Akocak Nabih Lolak Daniela Vullo Mustafa Durgun Claudiu T. Supuran |
| author_facet | Suleyman Akocak Nabih Lolak Daniela Vullo Mustafa Durgun Claudiu T. Supuran |
| author_sort | Suleyman Akocak |
| collection | DOAJ |
| description | A series of 20 histamine Schiff base was synthesised by reaction of histamine, a well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with substituted aldehydes. The obtained histamine Schiff bases were assayed as activators of five selected human (h) CA isozymes, the cytosolic hCA I, hCA II, and hCA VII, the membrane-anchored hCA IV and transmembrane hCA IX. Some of these compounds showed efficient activity (in the nanomolar range) against the cytosolic isoform hCA VII, which is a key CA enzyme involved in brain metabolism. Moderate activity was observed against hCA I and hCA IV (in the nanomolar to low micromolar range). The structure–activity relationship for activation of these isoforms with the new histamine Schiff bases is discussed in detail based on the nature of the aliphatic, aromatic, or heterocyclic moiety present in the aldehyde fragment of the molecule, which may participate in diverse interactions with amino acid residues at the entrance of the active site, where activators bind, and which is the most variable part among the different CA isoforms. |
| first_indexed | 2024-12-13T08:58:30Z |
| format | Article |
| id | doaj.art-387bbb09fb064bddaf03e10a9e1bedc7 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T08:58:30Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-387bbb09fb064bddaf03e10a9e1bedc72022-12-21T23:53:12ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742017-01-013211305131210.1080/14756366.2017.13866601386660Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activatorsSuleyman Akocak0Nabih Lolak1Daniela Vullo2Mustafa Durgun3Claudiu T. Supuran4Adiyaman UniversityAdiyaman UniversityUniversità degli Studi di FirenzeHarran UniversityUniversità degli Studi di FirenzeA series of 20 histamine Schiff base was synthesised by reaction of histamine, a well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with substituted aldehydes. The obtained histamine Schiff bases were assayed as activators of five selected human (h) CA isozymes, the cytosolic hCA I, hCA II, and hCA VII, the membrane-anchored hCA IV and transmembrane hCA IX. Some of these compounds showed efficient activity (in the nanomolar range) against the cytosolic isoform hCA VII, which is a key CA enzyme involved in brain metabolism. Moderate activity was observed against hCA I and hCA IV (in the nanomolar to low micromolar range). The structure–activity relationship for activation of these isoforms with the new histamine Schiff bases is discussed in detail based on the nature of the aliphatic, aromatic, or heterocyclic moiety present in the aldehyde fragment of the molecule, which may participate in diverse interactions with amino acid residues at the entrance of the active site, where activators bind, and which is the most variable part among the different CA isoforms.http://dx.doi.org/10.1080/14756366.2017.1386660Carbonic anhydrase activatorshistamineSchiff basesisozymesAlzheimer’s disease |
| spellingShingle | Suleyman Akocak Nabih Lolak Daniela Vullo Mustafa Durgun Claudiu T. Supuran Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators Journal of Enzyme Inhibition and Medicinal Chemistry Carbonic anhydrase activators histamine Schiff bases isozymes Alzheimer’s disease |
| title | Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators |
| title_full | Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators |
| title_fullStr | Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators |
| title_full_unstemmed | Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators |
| title_short | Synthesis and biological evaluation of histamine Schiff bases as carbonic anhydrase I, II, IV, VII, and IX activators |
| title_sort | synthesis and biological evaluation of histamine schiff bases as carbonic anhydrase i ii iv vii and ix activators |
| topic | Carbonic anhydrase activators histamine Schiff bases isozymes Alzheimer’s disease |
| url | http://dx.doi.org/10.1080/14756366.2017.1386660 |
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